The use of predictive and prognostic biomarkers paired with targeted cancer therapies may hold the key to reducing drug development time, improving drug efficacy, and guiding clinical decision making. While there are advances in cancer treatment, chemotherapy remains largely inefficient and ineffective. One reason for the generally poor performance of chemotherapy is that the selected treatment is often not closely matched to the individual patient's disease. A personalized medicine approach that couples precise diagnostics with therapeutics might alleviate this problem.
To date there are only a handful of biomarkers that have added value to clinical oncology practice. In part this is because perceived markers often are correlative but not causal to drug mechanism. Even when the “biomarker” biology does line up with the pharmacology of the companion therapy there is still significant challenge to predicting how a drug will work in a patient. Beyond this, the path to clinical development requires the participation of physician-scientists who see the value of the test and believe it can bring benefit to their patients.
The anti-apoptotic Bcl-2 family proteins are pivotal causal factors to cancer cell response to chemotherapy. Measurements of the functionality of these proteins in modulating mitochondrial apoptosis has proven to provide predictive biomarkers for cancer patient response to treatment. Many chemotherapies rely on apoptosis to be effective and in some cases modulation of apoptosis by a specific anti-apoptotic proteins correlates with responsiveness to particular therapy. The measurement of a particular protein then provides the biomarker for drug response. Accordingly, biomarkers that determine the expected response to a therapeutic agent continue to be sought after.